Molecular basis of mitochondrial DNA disease

J Bioenerg Biomembr. 1994 Jun;26(3):273-89. doi: 10.1007/BF00763099.


Mitochondrial ATP production via oxidative phosphorylation (OXPHOS) is essential for normal function and maintenance of human organ systems. Since OXPHOS biogenesis depends on both nuclear- and mitochondrial-encoded gene products, mutations in both genomes can result in impaired electron transport and ATP synthesis, thus causing tissue dysfunction and, ultimately, human disease. Over 30 mitochondrial DNA (mtDNA) point mutations and over 100 mtDNA rearrangements have now been identified as etiological factors in human disease. Because of the unique characteristics of mtDNA genetics, genotype/phenotype associations are often complex and disease expression can be influenced by a number of factors, including the presence of nuclear modifying or susceptibility alleles. Accordingly, these mutations result in an extraordinarily broad spectrum of clinical phenotypes ranging from systemic, lethal pediatric disease to late-onset, tissue-specific neurodegenerative disorders. In spite of its complexity, an understanding of the molecular basis of mitochondrial DNA disease will be essential as the first step toward rationale and permanent curative therapy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • DNA, Mitochondrial / chemistry
  • DNA, Mitochondrial / genetics*
  • Genotype
  • Humans
  • Metabolic Diseases / etiology*
  • Mitochondria / metabolism
  • Mitochondrial Myopathies / etiology*
  • Mutation
  • Optic Atrophies, Hereditary / etiology
  • Oxidative Phosphorylation
  • Phenotype


  • DNA, Mitochondrial